[A case of scleroderma associated with pancytopenia].
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Biomedical subjects
Publications and source records attributed to S Fujimoto.
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The crp gene of E. coli, which codes for cAMP receptor protein (CRP), has been cloned in the plasmid pBR322 on the basis of a genetic complementation. One of the recombinant plasmids, pHA1, was shown to direct the synthesis of CRP in a cell-free system. The location of the crp gene was determined by constructing subclones carrying various portions of pHA1. The nucleotide sequence of the crp gene has been determined. The coding region consists of 627 base pairs (bp), which specify a protein of 209 amino acids. The predicted amino acid sequence from the DNA sequence is consistent with the amino acid sequence partially known and the amino acid composition of CRP. After the coding region, there is a G-C rich inverted repeat sequence followed by a run of Ts, which could be a terminator of the crp gene. A possible promoter sequence was found about 180 bp upstream from the initiation codon and was shown to act as a promoter in vitro and in vivo. There are two dyad symmetry regions in a 167 bp leader sequence.
Incubation of isolated toad aortas in Ringer solution containing compound 48/80, a histamine liberator, resulted in marked degranulation of endothelial specific granules. Since incubation of these vessels in Ringer solution only did not show significant morphologic changes in these granules, these findings suggest that the degranulation was induced by histamine release from the granules, as in the case for mast cell degranulation, and that endothelial specific granules are a storage site of histamine in the toad aorta. The present morphologic data were supported by preliminary chromatography, which showed appreciable concentrations of histamine in the granule-containing pellets of subcellular fractions of homogenized toad aortas.
A remarkable increase in number of endothelial specific granules was observed in the rabbit umbilical veins between 2 and 5 days after birth. Electron microscopy indicated that the granules were segregated in the Golgi complex of the endothelial cells and released into the vascular lumen during the postnatal obliteration stage of this vessel. Incubation of the postnatal vessels in Ringer solution containing a histamine-releasing compound induced remarkable morphological alterations of these cytoplasmic components; a reduction of their osmiophilia, swelling with a widened space separating the granular matrix from the limiting membrane, fusion to each other and expulsion of their contents into the vascular lumen, as in mast cell degranulation by this drug, were noted. High-performance liquid chromatography of the homogenized vessels demonstrated appreciable concentrations of histamine in the postnatal samples. There was a correlation between the histamine concentration and the quantity of granules in the respective postnatal samples. The present study strongly suggests that the granules are reservoirs of histamine and have an important role in the obliteration of this vessel.
1,4-Dihydroxy-5,8-bis(((2-[(2-hydroxyethyl) amino] ethyl)amino))-9,10-anthracenedione dihydrochloride (mitoxantrone) was tested for antitumor activity against experimental tumors in mice and the results were compared with those of seven antitumor antibiotics: adriamycin (ADM), daunomycin (DM), aclarubicin, mitomycin C (MNC), bleomycin, neocarzinostatin, and chromomycin A3. The drugs were given IP or IV, in general on days 1, 5, and 9 following tumor inoculation. Mitoxantrone given IP at the optimal dose (1.6 mg/kg/day; as a free base) produced a statistically significant number of 60-day survivors (curative effect) in mice with IP implanted L1210 leukemia. The curative effect was not observed with any of the other antibiotics. In the case of IV implanted L1210 leukemia, there was an increase in lifespan (ILS) by more than 100% in the mice following IV treatment with mitoxantrone or DM. In IP implanted P388 leukemia, the curative effect was elicited by IP treatment with mitoxantrone or MMC. In IP implanted B16 melanoma, both the curative effect and a more than 100% ILS in mice that did die were produced by IP treatment with mitoxantrone or ADM. In SC implanted Lewis lung carcinoma, mitoxantrone and ADM administered IV also showed effective antitumor activities and produced a 60% and a 45% ILS, respectively. In conclusion, mitoxantrone and ADM had a wider spectrum of antitumor activity against mouse tumors, including two leukemias and two solid tumors, than did the other drugs; however, mitoxantrone elicited higher antitumor effects than ADM on mouse leukemias, especially on L1210 leukemias. Moreover, mitoxantrone possessed much higher therapeutic indices than ADM against IP implanted P388 (optimal dose/ILS40; greater than 128 versus 15.2) and L1210 (optimal dose/ILS25; 72.7 versus 4.8) leukemias. In addition, mitoxantrone showed moderate activity against DM-resistant L1210 leukemia.
A new water-soluble nitrosourea derivative, 1-(2-chloroethyl)-3-isobutyl-3-(beta-maltosyl)-1-nitrosourea (TA-077), was tested for antitumor activity against murine tumors and a human mammary carcinoma (MX-1) implanted in athymic mice, and the results were compared with those obtained with five other nitrosourea derivatives currently in clinical use: 1-(2-chloroethyl)-3-(methyl-alpha-D-glucopyranos-6-yl)-1-nitrosourea (MCNU), 1-(2-chloroethyl)-3-(beta-D-glucopyranosyl)-1-nitrosourea (GANU), 3-[(4-amino-2-methyl-5-pyrimidinyl) methyl]-1-(2-chloroethyl)-1-nitrosourea hydrochloride (ACNU), chlorozotocin, and 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea (Me-CCNU).
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1. Activities, contents and true specific activities of superoxide dismutase (SOD) were determined in human erythrocytes of 105 normal healthy subjects. 2. The mean SOD activity assayed by the inhibition of xanthine autoxidation was 11.0 x 103 units/g of haemoglobin (Hb). 3. The mean SOD content assayed by an immunochemical method was 456 micrograms/g of Hb. 4. Both activity and content of SOD showed normal distributions, and no significant variations with regard to sex and age were detected. 5. A highly positive correlation between activities and contents of SOD was observed in normal healthy subjects (r = 0.77, P less than 0.001). 6. True specific activity was calculated from levels of activity and content of SOD. The mean true specific activity of SOD in human erythrocytes was 23.7 units/micrograms of SOD. 7. There was no significant difference in true specific activity between young and old subjects.
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The absorption, distribution, excretion, metabolism and protein binding of orally administered tritium-labeled aspirin-isopropylantipyrine (AIA) were demonstrated in rats. 3H-AIA having 0.1 micro Ci/mg of specific activity and 93.2% of radiochemical purity was prepared by the Wilzbach's method. When 3H-AIA was administered orally to rats, about 20% of the given 3H was absorbed from gastro-intestinal tracts in 30 min and about 50% in 3 h, 72% of the dose was excreted in the feces and urine during 5 d, and 10% was excreted in the bile in 24 h. The highest accumulation of 3H in most organs was found in one to three hr after oral administration and 3H was concentrated in the liver. THe major metabolites excreted in urine within 24 h after administration were salicylic acid-isopropylantipyrine (SIA) sulfate (57.7%) and SIA glucuronide (30.5%). The amount of free SIA excreted in urine was 1.2%. The carboxylamide bond of AIA was never cleaved in vivo to give salicylic acid and 3-aminomethylisopropylantipyrine. About 58% of 3H in blood 1 h after the administration was found with serum protein.
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By administration of p-chlorophenylalanine (PCPA), a synthetic inhibitor of 5-hydroxytryptamine (5-HT), to rabbits, granular vesicles in the taste receptor cells remarkably decreased their contents. The recovery of this core substance depletion occurred in specimens killed on the 15th day after injection of the drug and in animals injected with 5-hydroxytryptophan (5-HTP) after treatment with PCPA. Electron microscope observation suggests that granular vesicles in the receptor cells are 5-HT-storing particles and favors the view based on recent fluorescence histochemistry which indicates the presence of a biogenic monoamine, presumably 5-HT, in rabbit foliate taste bud cells.
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The authors have studied the effect of acute intracranial hypertension produced by placement of an epidural balloon (control group) in cats, on cerebral perfusion, evoked responses, and hematological parameters. These elements were measured in similarly injured animals which underwent isovolemic hemodilution with dextran 75, after relief of intracranial hypertension. Four hours after balloon deflation, perfusion was markedly impaired in 30% of the control group, and was reduced to 11% in the dextran-infused group. The suppressed N1 amplitude of somatosensory evoked responses on the compression side, the reduced platelet aggregability, and the erythrocyte-deformability by intracranial hypertension were all significantly more restored in the dextran-infused group after decompression. The percentage of platelets with volumes between 21.75 and 48.75 cu mu (normal 9.75 to 12.75 cu mu) significantly increased after decompression. Activation of platelets during intracranial hypertension leads to an increase in platelet volume from platelet aggregation, and correlates with a decrease in platelet aggregability. It was also suggested that reduction of erythrocyte deformability was not caused by erythrocyte aggregation. The authors emphasize the role of intravascular factors such as vascular obstruction by platelet aggregates, and difficulty in passage of erythrocytes through capillaries due to reduced deformability, in the disturbance of the microcirculation following acute intracranial hypertension. The protective effect of dextran 75 by inhibition of platelets as well as hemodilution is stressed.